Manufacture of the isomeric monoethyl ethers of protocatechuic aldehyde



April 14, 1931.

F. BOEDECKER MANUFACTURE OF THE ISOMERIC MONOETHYL ETHERS 0FPROTOCATEGHUIC ALDEHYDE Filed NOV. 19, 1927 SoZuLzlon P @Caf/5 Inventorma@ ma@ Patented Apr. 14, 1931 UNITED STATES PATENT OFFICE FRIEDRICHBOEDECKEP., OF

BERLIN -DAHLEI'L GERMANY Application filed November 19, 1927, Serial No.234,557, and in Germany January 24, 1927.

vsimilar Way, owing to the fact that 1.l-propenyl-Li-ethoxy-diydroxybenzene is less solublethanl-propenyl--ethoxy-thydroxybenzene 2. The alkali metal salts as Wellas the acylated compounds of the 3-ethoxy-compound are less soluble thanthe corresponding lfethoxy-compound;

3. m-ethyl-protocatechuic aldehyde is soluble in alkali metal carbonatesolutions, in contradistinction to p-ethyl-protocatechuic aldehyde. p

Furthermore I have found that instead of safrol, camphor oil may be usedas starting Vmaterial, it being only necessary to treat the product ofthe splitting operation', after removal of the alcohol, with inertsolvents, whereby the substances accompanying the safrol'in the camphoroil, are completely re- `moved after having served as desirable diluentsduring the splitting operation.

`When treating the product obtained by splitting safrol or i-safrol withalcoholic alkali or an alcoholic alkali metal alcoholate solution,aft-er separation of the unchanged material-With ethylating means, forinstance, With an ethyl halogenide, and then heating the resultingmixtures with diluted acids, preferably in alcoholic solution, a mixtureof the two isomeric propenyl-pyrocatechine-mono-ethyl ethers isobtained.

For better comprehension the steps of the process are illustrated in theannexed drawing which is self-explanatory.

Emeril/ple 1 1 kilogram of safrol is heated with 3 liters ofmethylalcoholic caustic potash solution in a. stirring-autoclave to13C-140o C. for about 2O hours. Then the methyl alcohol is disstilledoff, the residue dissolved in a little Water, and the solution extractedby shaking it with benzene. The benzene solution on distilling oli thesolvent leaves 30 grams of a residue consisting of i-chavibetol. Fromthe remaining aqueous-alcoholic solution an oil is separated byacidifying substantially consisting of a mixture of pandm-propenylpyrocatechine-mono-methoxy-methyl ether oemcgnonoom. 175 gramsof this mixture are dissolved in about e. c. of an ethyl-alcoholiccaustic potash solution of about 9%; 10() grains of ethyl bromide areadded and the whole is heated in an autoclave to about O C. for 3 hours.Then the alcohol is distilled oli' and the residue dissolved in waterand ether. The ethereal solution is washed with diluted caustic sodasolution to remove a little quantity of the non-ethylated product. Afterdistilling od the ether, the mixture of both the ethyl others distillsat 163465O C. (13 mm.) as a nearly colorless oil. The output amounts to185 grams.

From thn alkaline Washing Water about 8 grams of the non-ethylated bodymay be recovered.

grams of the ethyl ether mixture are dissolved in 1.1 liter of alcoholand, after the addition of 150 c. c. of water and some drops of 25%hydrochloric acid, the solution is refluxed for about 6 hours. Then thealcohol is distilled oft and the remaining oil is dissolved in ether. For removing the remaining` small amount of the unsaponified product theethereal solution is extracted with diluted caustic soda solution andthe phenols are again precipitated from the alkaline solution byacidulating. They are dissolved in ether, the solution is dried and,after evaporating the ether, the residue is distilled in vacuo. 125grams of an oil boiling at 148-152o C. (14 mm.) and solidifying in thecold to a crystalline mass are obtained. rlhe oil smells similar toeugenol,

The resulting mixture may be oxidized in the well-known manner to thecorresponding aldehydes which may be separated into the isomers by meansof an alkali metal carbonate as above mentioned.

Now it is possible to nearly completely work up the mixture of the twopropen 7lpyrocatechine-mono-ethyl ethers to obtain the more valuablecompound in which the ethoxygroup is in meta-position to thepropenylgroup, and which on oxidation is transformed into the m-ethylether of protocatechuic aldehyde. A practical way of operatingy is asfollows:

Firstly the p-compound of higher fusingpoint is separated from theabove-mentioned mixture by freezing-out and transformed into thedi-ethyl ether by Ytreating the same with ethylating means, such asdi-ethyl sulfate or an ethyl halogenide &c. On heating the di-ethylether with an aqueous or alcoholic alkali solution, preferably at atemperature between 100 and 1500 C. again a mixture of both mono-ethylethers is obtained. The best output however is obtained by usingsolutions of alkali metal alcoholates in strong, preferably absolutealcohol. In this case not only a far smaller excess of splitting` agentis needed which is to be recommended in any case, but moreover `theoutput is considerably increased, so that advantages obtained in twodirection From the resulting` mixture the main quantity of the p-conpound may be separated by freerinn` out above described. By againsubjecting mixture to the above described operation, preferably togetherwith the p-compound firstly separated from the mixture in the nextbatch, the p-compound may by degress almost wholly converted into them-compound..

The working-up of the product contained in the filtrates after theremoval of the pethylepropenyl-pyrocatechine ether is now ac lcomplished by transforming the product into its acyl-compoundscontaining the benzoyl radical or derivatives thereof, as, for instance,the nit-robenzoyl group. ln this case the .conditions of solubility arequite reversed as compared with those of the free phenol ethers, thesaid acyl-compounds of the m-ethyl ether being less soluble than thoseof the pcompound. Therefore it is possible, for instance byrecrystallizing the benzoylated raw products, preferably fromhydrocarbons,to obtain a quite purep-benzoyl-m-ethyl-propenylpyrocatechine having a fusing-point of 890 C.which on saponification with an alkali yields the free phenol ether.

The raw product of the m-ethyl ether of propenyl-pyrocatechine may alsobe puried by the way of its sodium salt. I have ascertained that thealkali metal salts of the propenyl-pyrocatechine ether, ethylated iniii-position tothe propenyl group, are less soluble in water, alcohol&c. than the corresponding p-compound. Therefore the msubstituted ethermay be separated from a solution containing the said phenols (and, toall appearances, still further isomers) in the form of an alkali metalsalt, after `the main quantity of the propenyl-pyrocatechine-p-ethylether has been frozen out.

Example 2 the phenol mixture obtained '123 grams of disuct may berecovered by recrystallization from hexahydrotoluene, showing afusingpoint of 84-85o C. Fusing-point of the acetate (iS-690 C., of thebenzoate (S0-610 C. y rlllie mother liquor is freed` from the solventand the residue dissolved by heating withy 180 c. c. of a 10% causticsoda solution. n On cooling down, a sodium salt crystallizes out; thisis filtered off by suction, washed with diluted sodium chloride solutionand recrystallized anew from water from which it comes out in vlongneedles. It is dissolved in water, decomposed by diluted acid, absorbedin other, dried and subjected to distillation. lloiling-point 145O C.(13 min). The fusingpoint of the recrystallized product is o C. Output45 grams. Fusing-point'of the benzoate 890 C., of the kacetate 39-41O C.

From the mother liquors of the sodium salt a third fraction is recoveredby acidulating from whichl another small lportion of the p-ether may beobtained by means of hexahydrotoluene. i i y The solution resulting fromthe yseparation of the propenyl-pyrocatechine-m-methyl ether in the formof its alkalimetal salt produces, on acidulating, an oil amounting toabout one fifth of the treated mixture of the m-and the p-ether. Howeverl did not succeed, even with theabove-described operations, inseparatingtherefrom the two propenyl-pyrocatechine ethers after freezing out theremainders of the p-ethyl ether. |This may be due to the presence of'further (probably cisand transisomeric) 'compounds. I have nowdiscovered the surprising fact that the desired result can be attainedby ethylating the mixture of phenols in question and splitting thethoroughly ethylated product by heating it with an alkali. From theresulting reaction product both the mas Well as the p-ethyl ether ofpropenyl-pyrocatechine can easily be obtained according to the methoddescribed in the foregoing paragraph. Again a non-crystallizable oilamounting' to about one fifth of the starting material is obtained Whichmay be treated in the above-described manner, preferably7 together Witha fresh batch, to obtain the two isomers. In doing this it is notnecessary to start from the oil itself, but, for instance, whenethylating with diethyl sulfate I may start directly with the solutionresulting from the separation of the difficultly soluble sodium salt.

It it is desired to obtainmerely propenyll-hydroxy-S-ethoxy-l-benzene orthe p-ethyl ether of the protocatechuic aldehyde the liltrate obtainedafter freezing out the p-ether from mixtures containing both isomers isWorked up in the manner above-described for treating the p-ether with aView of obtaining the m-isomeric compound, that is to say bytransforming the product into the diethyl ether and decomposing thelatter to a mixture of hydroxy-3-ethoxy-4- and ethoxy-B-hydroxy--propenyl-l-benzene Which may be treated again as abovedescribed.

'Ihe propenyl p yrocatechine mono ethyl ethers are transformed in theWell-known manner by means of suitable oxidants such as ozone into thetwo ethyl ethers of protocatechuic aldehyde.

As already mentioned, camphor oil may be used as starting materialinstead of safrol in connection With the here described process. F orinstance, When 800 parts, by Weight, of camphor oil containing 60% ofsafrol are treated with 480 parts o-f caustic soda and 1000 parts ofmethyl alcohol in the manner above described for safrol, 400 parts ofthe methoxy-methyl ether mixture are obtained on acidulating, after 360parts of products insoluble in alkalies have previously beenWithdrawnfrom the 4solution by means of benzene. These insolubleproducts substantially consist of the hydrocarbons contained in camphoroil besides about 0% of safrol. The methoxy-methyl ether mixture isfurther treated according to the above-described methods.

I claim 1. Process of producing the -ethyl ether of protocatechuicaldehyde, comprising treating I-Q-dihydroxybenzene methylene ethersubstituted in the l-position by a umvalent unbranched alkylene radical@3l-I5 elevated temperatures With alcoholic alkali, ethylating thereaction product, removing from the resulting mixture of thepropenylorthodihydrobenzene-monoethyl ethers the 4 propenyl 1,2dihydroxybenzene- 1 -ethyl ether by freezing out, converting theremaining more soluble propenyl-orthodihydroxybenzene monoethers intotheir alkali metal salts, thereby removing rom them the less solublealkali metal salt of the fl-propenyll,2-dihydroxybenzene-Q-ethyl ether,decomposing the said salt by an acid and oxidizing the resultingl-propenyl-1,2-dihydroxybenzene-Q-ethyl ether to the S-ethyl ether ofprotocatechuic` aldehyde.

2. Process of producing the 3-ethyl ether of protocatechuic aldehyde,comprising treating l-Q-dihydroxybenzene methylene ether substituted inthe l-position by a uniialent unbrauched alkylene radical CBI5 atelevated temperatures with alcoholic alkali, ethylating the reactionproduct, removing from the resulting mixture of thepropenylorthodihydroxybenzene-monoethyl ethers the4-propenyl-l-inonoethyl ether by freezing out, converting the remainingmore soluble propenyl orthodhydroxybenzene-monoethers into their alkalimetal salts, thereby removing from them the less soluble alkali metalsalt of the l-propenyl-Z-ethyl ether and decomposing the said salt by anacid, ethylating the remaining mixture of propenyl orthodihydroxybenzene -monoethylethers, heating With alcoholic alkali,acidulating, again returning the remaining mixture into the process, andoxidizing the 4- propenyl-l,2-dihydroxybenzene-Q-ethyl ether to thefl-ethyl ether of protocatechuic aldehyde.

8. Process of producing the 3-ethyl ether of protocatechuic aldehyde,comprising treating l-Q-dihydroxybenzene methylene ether substituted inthe 4-position by a univalent unbranched alkylene radical 03H5 atelevated temperatures with alcoholic alkali, ethylating the reactionproduct, removing from the resulting mixture of thepropenylort-hodihydroxybenzene-monoethyl ethers thel-propenyl-l-monoethyl ether by freezing out, converting thepropenyl-orthodihydroxybenzene monoetliers into their alkali metal sals,thereby removing from them the less soluble alkali metal salt of the4pro penyl-P-ethyl ether, and decomposing the said salt by an acid,ethylating the remaining mixture ofpropenyl-orthodihydroxybenzenemonoethyl ethers and the saidl-propenyl-lmonoethyl ether, heating with alcoholic alkali, acidulating,again returning the remaining mixture into the process, and oxidizingthe l-propenyl-l,Q-dihydroxybenzene-Q-ethyl ether to the l-ethyl etherof protocatechuic aldehye.

4. In the process of producing the -ethyl ether of protocatechuicaldehyde, the steps comprising treating l-Q-dihydroxybenzene methyleneether substituted in the 4-position by a univalent unbranched alkyleneradical (13H5 at elevated temperatures with alcoholic ici alkali,ethylating the reaction product, removing from the resulting mixture ofthe propenyl-orthodihydroxybenzene-monoethyl others the4-propenyl-l,Q-dihydroxybenzene- 1i-ethyl ether by freezing out,converting the remaining more solublel propenyl-orthodihydroxybenzenemonoethers into their alkali metal salts, thereby removing from them theless soluble` metal salt of the i-propenyl-LQ- dihydroxybenzene-Q-ethylether, and decomposing the said salt by an acid.

5. Process of producing the S-ethyl ether of protocatechuic aldehydecomprising treating camphor oil WithY alcoholic alkali, removing thealcohol, extracting the product after addition of Water with an inertsolvent,

.treating the mixture of phenolethers with ethylating means, removingfrom the resulting mixture of the propenyl-orthodihydrobenzene-monoethylethers the l-propenyl-LQ- -dihydroxybenzene-l-ethyl ether by freezingout, converting the remaining more solublepropenyl-orthodihydroxybenzene monoethers into their alkali mei alsalts, thereby removing from them the less soluble alkali `metal salt ofJthe t-propenyl-l,Q-dihydroxybenzene-Q-ethyl ether, decomposing the saidsalt by an acid and oxidizing the resultingipropenyl-l,2-dihydroxybenzene-Q-ethyl ether to the 3-ethyl etherV oflprotocatechuic aldehyde.

6. Process of producing the S-ethyl ether of protocatechuic aldehyde,comprising treating l-Q-dihydroxybenzene methylene ether substituted inthe d-position by a univalent unbranched alkylene lradical 08H5 atelevatedtemperatures With alcoholic alkali, ethylating the reactionproduct, removing from the resulting mixture of the propenyl-,catecliuic aldehyde.

7. Process of producing the 3-ethyl ether of protocatechuic aldehyde,comprising treating 1-2-dihydroxybenzene methylene ether substituted inthe Ll-position by a univalent inbranched alkylene radical 03H5 atelevated temperatures with alcoholic alakli, ethylat- 'ing the reactionproduct, removing from the resulting mixture of the propenyl-orthodi-Vhydroxybenzene-monoethyl ethers the 4i-propenyl-l-monoethyl ether byfreezing out,

converting the Apropenyl-orthodihydroxybenzene monoethers into theiralkali meta-l salts, thereby removing from them the less soluble alkalimetal salt of the 4-propenyl-2-ethyl ether, and decomposing the saidsalt by an,

acid ethylating the remaining mixture ofpropenyl-orthodihydroxybenzene-monoethyl ethers and the saidt-propenyl-l-monoethyl ether, heating With alcoholic alkali metalalcoholate solution, acidulating, again returning the remaining mixtureinto the process, and oxidizing thet-propenyl-l,EZ-dihydroxybenzene-Q-ethyl ether to the -ethyl ether ofprotocatechuicv aldehyde.

8. As a new composition of matter, an equimolecular m'xure of tWoisomeric phenol ethers having the formulaei-alkoxymethoxy-3-ethoxy-l-prcpenylbenzol, and 4ethoxy-3-alkoxymethoxy-l-propenylbenzol.

9. As a new composition of matter, an equimolecular mixture of tvvoisomeric phenol ethers having the formulae*d-ethoxy-)l`hydroxy-l-propenylbenzol and 24e-hydroxy?)` ethoxy-l-propenylbenzol.

ln testimony vvhereofl affix my signature.

FRIEDRICH BOEDECKER.

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